A man in his 60s presented for further evaluation of a right inguinal and scrotal lesion (Figure 1). The rash initially started 4 years prior as a dime-sized, pink, scaly area in the right inguinal crease and was pruritic. Results of a biopsy at the time were consistent with lichen simplex chronicus, and treatment with topical steroids was initiated. Since then, the rash had failed to resolve and the affected area had increased in size to its present dimensions. The patient had a history of prostate cancer treated with prostatectomy 4 years previously without evidence of recurrence and melanoma of the posterior neck treated with wide local excision, in addition to non–insulin-dependent diabetes mellitus and hyperlipidemia controlled with oral medications. He does not smoke and has been in a monogamous marriage for more than 30 years. Examination revealed a multifocal scaly, pink-red beefy plaque in the right inguinal crease extending from the superior aspect of the scrotum to the gluteal crease measuring approximately 6 × 7 cm in total area with some areas of excoriation and superficial open wounds. An additional area of macular erythema extended superiorly along the inguinal crease toward the medial thigh. No lymphadenopathy of the inguinal region was noted.
Extramammary Paget disease
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B. Extramammary Paget disease
Repeated biopsy revealed epidermal infiltration by Paget cells, which are large vacuolated cells with vesicular nuclei and foamy pale cytoplasm (Figure 2).1 Immunohistochemical stains were positive for cytokeratin 7 and carcinoembryonic antigen and negative for prostate-specific antigen and S100 protein.2 These findings are pathognomonic for extramammary Paget disease (EMPD) and distinguish it from Bowen disease, or squamous cell carcinoma in situ, which typically arises in the penis and appears as a gradually enlarging, well-demarcated, velvety plaque.3 Human papillomavirus infection is a risk factor. Cells are typically cytokeratin 7 and carcinoembryonic antigen negative and p63 positive. Lichen sclerosis, a chronic inflammatory skin disease characterized by atrophic white plaques,3 typically occurs women’s anogenital area but has been reported in men and children and is treated with topical corticosteroids.4 Histologic features include a thinned epidermis; inflammation and altered fibroblast function lead to fibrosis of the papillary dermis.3 In a diabetic patient with a persistent rash nonresponsive to steroids, a fungal infection such as candida or tinea cruris can persist in the absence of antifungal therapies and be diagnosed by fungal culture.
Extramammary Paget disease is an intraepithelial neoplasm affecting areas rich in apocrine sweat glands. Whereas Paget disease occurs most often in the nipple, EMPD is most common in the vulva of women and penoscrotal area of men 50 to 80 years old. It is usually associated with pruritus and has an insidious onset, presenting as an erythematous, pruritic plaque that may become ulcerated, scaly, or eczematous. Many patients are treated for eczema for years prior to definitive diagnosis. Other differential diagnoses include superficial spreading melanoma, neuroendocrine carcinoma, mycosis fungoides, psoriasis, leukoplakia, eczema, or intraepidermal spread of visceral carcinoma.2
Surgery is the standard treatment for EMPD, with an emphasis on obtaining negative margins to control the disease.1,2,5 Intraoperative frozen sections and Mohs surgery have been used to decrease the positive margin rate and risk of recurrence with good results.6 The extent of resection required to obtain negative margins is often much greater than the visible area of involvement of the disease, and frozen sections must be systematically performed. Workup should also include a computed tomographic scan of the abdomen and pelvis because EMPD may be associated with an underlying abdominal or genitourinary cancer (ie, colorectal, prostate, bladder, or kidney), although the frequency of this association is not consistently reported.1,2 Some centers also screen for a secondary cancer with chest x-ray, cystoscopy, colonoscopy, and serum prostate-specific antigen level. Lymph node dissection is indicated if clinical or pathologic lymph node metastases are present, and sentinel lymph node biopsy can be considered in cases of invasive disease.7 Hegarty et al1 reported a difference in median survival in patients with invasive disease compared with those with intraepidermal EMPD of 14.5 vs 55 months, respectively. Although the optimal regimen and timing have not been established, tumor responses have been described with several chemotherapy agents including mitomycin, vincristine sulfate, cisplatin, fluorouracil, and docetaxel for invasive disease.5 Radiation therapy is considered an alternative treatment when there are contraindications to surgical excision or when patients decline surgery. However, due to varying reports of effectiveness, its utility as a monotherapy is uncertain.8,9
In summary, patients with pruritic, macular plaques unresponsive to topical therapies should undergo biopsy for definitive diagnosis. A benign initial diagnosis but worsening symptoms should prompt repeated biopsy. Once EMPD is diagnosed, an underlying cancer should be ruled out and surgical excision scheduled.
Our patient underwent wide local excision with frozen section margin control with a scrotal advancement flap for reconstruction. Final pathologic analysis revealed focal microinvasion (depth, <0.5 mm) with negative margins.
Corresponding Author: Jeffrey H. Kozlow, MD, MS, Section of Plastic Surgery, Department of Surgery, University of Michigan, 1500 E Medical Center Dr, 2130 Taubman Center, SPC 5340, Ann Arbor, MI 48109-5340 (email@example.com).
Published Online: February 19, 2015. doi:10.1001/jamaoncol.2014.260.
Conflict of Interest Disclosures: None reported.
Ballard TNS, Montgomery JS, Kozlow JH. Inguinal and Scrotal Lesion. JAMA Oncol. 2015;1(1):107-108. doi:10.1001/jamaoncol.2014.260